Pathology International

doi: 10.1111/pin.13243pmid: N/A

Sano, Daisuke; Kihara, Takako; Yuan, Jiayin; Kimura, Neinei; Ohkouchi, Mizuka; Hashikura, Yuka; Ohkubo, Shuichi; Hirota, Seiichi

doi: 10.1111/pin.13315pmid: 36825754

Approximately 40 families with multiple gastrointestinal stromal tumors (GISTs) and germline c‐kit gene mutations have been reported. Three knock‐in mouse models have been generated, and all the models showed a cecal GIST. In the present study, we established a cell line derived from cecal GIST in a familial GIST model mouse with KIT‐Asp818Tyr. Since the established cells showed spindle‐shaped morphology with atypical nuclei, and since immunohistochemistry revealed that they were positive for α‐SMA but negative for KIT, CD34 and desmin, the phenotypes of the cells were reminiscent of dedifferentiated GIST‐like ones but not the usual GIST‐like ones. Gene expression analysis showed that the cell line, designated as DeGISTL1 cell, did not express c‐kit gene apparently, but highly expressed HSP90 families and glutaminase 1. Pathway analysis of the cells revealed that metabolic pathway might promote their survival and growth. Pimitespib, a heat shock protein 90α/β inhibitor, and Telaglenastat, a selective glutaminase 1 inhibitor, inhibited proliferation of DeGISTL1 cells and the combination of these showed an additive effect. DeGISTL1 cells might be a good model of dedifferentiated GISTs, and combination of Pimitespib and Telaglenastat could be a possible candidate for treatment strategy for them.

Higashiyama, Masahiro; Motoi, Noriko; Yotsukura, Masaya; Yoshida, Yukihiro; Nakagawa, Kazuo; Yagishita, Shigehiro; Shirasawa, Masayuki; Yoshida, Tatsuya; Shiraishi, Kouya; Kohno, Takashi; Ohe, Yuichiro; Watanabe, Shun‐ichi

Yanagita, Emmy; Yamada, Hiroshi; Kobayashi, Tetsuro; Aimono, Eriko; Nakamura, Kohei; Hirasawa, Akira; Nishihara, Hiroshi

doi: 10.1111/pin.13318pmid: 36971494

The acquisition of high‐quality biospecimens and the appropriate handling of these materials are indispensable for successful clinical sequencing. We developed a cancer clinical sequencing system targeting 160 cancer genes: PleSSision‐Rapid. Through the PleSSision‐Rapid system, we have analyzed DNA quality evaluated by DIN (DNA integrity number) with 1329 formalin‐fixed paraffin embedded (FFPE) samples including 477 prospectively collected tissues for genomic test (P) and 852 archival samples after routine pathological diagnosis (A1/A2). As a result, the samples with more than DIN 2.1 was 92.0% (439/477) in prospectively collected sample (P), while it was 85.6% (332/388) and 76.7% (356/464) in two types of archival samples (A1/A2). We performed the PleSSision‐Rapid sequence using the samples with over DIN 2.1 and DNA concentration >10 ng/μL with which we were able to construct a DNA library, and the probability of sequence success was almost equivalent during all types of specimen processing, at 90.7% (398/439) in (P), 92.5% (307/332) in (A1) and 90.2% (321/356) in (A2), respectively. Our result indicated the clinical benefit to prepare the prospective collection of FFPE materials for indisputable clinical sequence, and that DIN ≥ 2.1 would be a solid parameter for sample preparation of comprehensive genomic profiling tests.

Murata, Shin‐ichi; Matsuzaki, Ibu; Kishimoto, Mitsuo; Katsuki, Naomi; Onishi, Toshinori; Hirokawa, Mitsuyoshi; Kojima, Fumiyoshi

doi: 10.1111/pin.13323pmid: 37042564

Papillary thyroid carcinoma (PTC) is usually indolent; however, some rare subtypes of PTCs, such as columnar cell and hobnail subtypes, carry poor prognosis as an intermediate malignancy between differentiated carcinoma and anaplastic carcinoma. We present the case of a 56‐year‐old Japanese woman having PTC with aggressive behavior showing characteristic histological features of a predominantly fused follicular and focally solid (FFS) pattern. The fused follicular pattern is cribriform‐like without intermingled vessels. This PTC with FFS pattern included frequent mitotic figures, necrosis, lymphovascular invasion, and metastases with high clinical stage. The tumor cells were broadly positive for antibodies to TTF‐1, PAX8, and bcl‐2, and negative for cyclin D1. Ki‐67 labeling index was approximately 10%, and there was occasional positivity of p53. Targeted next generation sequencing analysis only detected a NRAS mutation (Q61K); there was no mutation and no translocation of other genes including BRAF and RET/PTC. To our knowledge, this is first report that PTC shows aggressive FFS growth pattern. The tumor is possibly included in the new category of differentiated high‐grade thyroid carcinoma in the World Health Organization 2022 classification, or in a novel subtype of PTC owing to its characteristic histological feature and intermediate malignancy between differentiated carcinoma and anaplastic carcinoma.

Maekawa, Kazunari; Kuroki, Daisuke; Hamada, Takeomi; Kushima, Ryoji; Sato, Yuichiro; Yamashita, Atsushi

doi: 10.1111/pin.13319pmid: 36970951